This invention relates to the field of organic chemistry and more particularly to 5-gluconamido-2,4,6-triiodo-N-methylisophthalamic acid, 3-acetamido-2,4,6-tiiodo-5-trishydroxymethylacetamido-benzoic acid, related compounds and certain salts, esters and acyl halides thereof. The acids, salts and esters are useful as x-ray contrast agents.
Many 2,4,6-triiodobenzoic acid derivatives have been proposed for use as x-ray contrast agents. These include, as a subgroup, many 2,4,6-triiodoisophthalamic acid derivatives such as 5-acetamido-2,4,6-triiodo-N-methylisophthalamic acid and its salts (G. B. Hoey, U.S. Pat. No. 3,145,197 (1964). The coined terms "iothalamic acid" and "iothalamate" have been applied to these compounds. A profuse literature relating to the radiological uses of these compounds have been published in succeeding years.
Certain N-hydroxyalkyl-2,4,6-triiodoisophthalamic acids have also been disclosed. For example, Guerbet U.S. Pat. No. 3,622,616 and Salvesen et al. U.S. Pat. No. 3,702,866 disclose 5-acetamido-N-(2-hydroxyethyl)-2,4,6-triiodoisophthalamic acid. In addition, Salvesen et al. also disclose the compound N-(3-acetamido-5-carboxy-2,4,6-triiodobenzoyl)-N-methylglucamine which may also be designated 5-acetamido-N-(D-gluco-1-deoxy-2,3,4,5,6-pentahydroxyhexyl)-2,4,6-triiodo- N-methylisophthalamic acid.
Further, Almen et al. (U.S. Pat. No. 3,701,771) disclose a considerable number of non-ionic N-(2,4,6-triiodobenzoyl)-amines said to be useful as x-ray contrast agents in the cerebrospinal cavities, including one (compound 41) derived from tris (hydroxymethyl) aminomethane. This compound is designated as N-[3-N-methylacetamido-5-N-(beta-hydroxyethyl)-acetamido-2,4,6-triiodobenz oyl] N-[tris(hydroxymethyl)-methyl] amine. This compound was reported to have a rather low water solubility (0.86%) although many other compounds in the series were disclosed to be relatively highly soluble in water.
The use, as x-ray contrast media, of aqueous solutions of salts of various 2,4,6-triiodoisophthalamic and other 2,4,6-triiodobenzoic acids with pharmaceutically acceptable cations such as sodium, calcium and magnesium and alkanolamines such as ethanolamine, diethanolamine and meglumine (N-methylglucamine) is well known to those skilled in the art.